| Bronchopulmonary dysplasia (BPD) is the most common cause of morbidity in prematurely born infants who require prolonged mechanical ventilation. Patients is often associated with long-term pulmonary and/or neurodevelopmental disability or death in severe cases. The morbidity of BPD is raising,though the severity of respiratory distress syndrome has been reduced with antenatal corticosteroid therapy, which hastens lung development, and postnatal replacement surfactant treatment. Lack of large-scale clinical data and BPDdiagnostic criteria that cause the incidence of BPD varies greatly in reports. The etiology of BPD is likely multifactorial, including oxygen toxicity, infection, mechanical ventilation, patent ductus arteriosus, and inflammation, revealing its high-risk factors play role in the clinical diagnosis, treatment and prognosis. In the paper, we collected medical data, to reveal the risk factors, and elucidate the molecular mechanism of development and progression of BPD and a target for early diagnose, therapy.The main pathological changes of BPD are alveolar structural damage, pulmonary fibrosis and substantial thickening of alveolar surface area reduction and near the end of the airway alveolar regions increase the density of capillaries. BPD is difficult to be cured, and the lack of radical treatment, explore its pathological mechanism, in search of better treatment has been the urgent need to solve problems. Study found that in BPD in bronchoalveolar lavage fluid or lung tissue of transforming growth factorβ1 (TGF-β1) expression was significantly higher. Many studies have shown that TGF-β1 influence lung development, but also in immature lung fibrosis in high-oxygen injury in the process of development plays a very important role. Therefore, TGF-β1 of hyperoxia-induced lung injury become today's research focus. Animal experiments have been reported in the literature, but the human experiment is less relevant research reports. We have collected serum from premature children with high-risk factors of BPD and lung tissues after death to study the changes in TGF-β1, in order to lay the foundation for molecular treatment of BPD.Charpter one Bronchopulmonary dysplasia risk factor analysis and prognosisObjective:To study the incidence and risk factors of bronchopulmonary dysplasia (BPD),revaling the risk factors of BPD.Methods:Eight hundred and eighty-five prematures with gestational age less than 37 weeks and surviving no less than 28 days were enrolled in the study, from January 1st 2007 to December 31 2009. One hundred and sixty-one prematures with BPD were compared to seven hundred and twenty-four prematures without BPD in terms of sex, gestational age, birth weight,twins or multiplets,mode of production,length of stay,cost of hospitalization complication,ventilator parameter, length of use ventiator, number of times,length of use nCPAP,length of use oxygen, blood gas analysis of primary,routine and biochemistry of blood test,usage of prenatal steroids, usage of postnatal surfactant, complication of gestation and prognosis. The key factors of BPD were analyzed and made the multi-independent variable regression analysis to its high-risk factor, promulgates independent factor which BPD occurs. Measurement data was represent by mean±standard deviation, quantitative data was analyzed by t-test; count data was analyzed bu x2 test, multivariate analysis was analyzed by Logistic regression analysis, The difference was deemed statistically significant at P<0.05, all data was used by SPSS16.0.Results:1.The incidence of BPD in hospital date number≥28 was 18.2% (161/885). The overall incidence of BPD in preterm newborns was 3.6%.2. BPD incidence of hospitalized children with≥28 day reduced (about 4.1%/ year), the total incidence rate increased year by year (about 0.6%/year) from 2007-2009. 3.The single factor analysis demonstrated that the BPD high-risk factor had the sex (male), gestational age(<30weeks),birthweight(<1400g), mode of production (natural delivery), multiplets, NRDS, PDA, PPHN, pneumorrhagia, pneumothorax, pneumonia, intracranial hemorrhages, cardiac dysfunction, septicemia, anemia, HIE, oxygen concentration(≥40%), length of use ventiator (≥10days), number of times (≥one time), length of use nCPAP(≥10days), PH<7.10,hypoproteinemia (≤30.0g/L) and asphyxia(mild).4.Multivariate logistic analysis revealed that gestational age less than 30 weeks, mechanical ventilation time and number of times,cardiac dysfunction,nCPAP time were independent risk factors for BPD (P<0.05),the correlation coefficients were 1.128,0.996, (0.216,1.089,4.102), (2.665,4.144),4.004,3.790, respectively. OR values were 3.089, 2.708,1.242,2.972,60.469,14.370,63.031,44.273, respectively.5. Prenatal hormones did not reduce the incidence of BPD.6.The incidence of BPD had no significant relationship with pregnancy complications.7.BPD group of children with retinopathy of prematurity, congenital cataracts, hydrocephalus, congenital heart disease, genetic metabolic diseases, central nervous system infections were higher than the non-BPD group, and give up/mortality was significantly higher than the non-BPD group; BPD group has significantly worse prognosis than non-BPD group.Conclusion:1. Gestational age<30 weeks is the basis of the occurrence of BPD.2BPD incidence increased year by year, the prenatal factors on the occurrence of BPD was no significant;3.BPD treatment difficult and prognosis is poor, there are risk factors for premature children, integrated control measures should be applied,such as anti-infection, reduce the time of ventilator use, prevention and treatment of heart failure, etc. Charpter two The changes of TGF-β1 protein expression and significance with BPD childrenObjective:To study the expression of TGF-β1 protein in BPD children' serum and lung tissue to explain its roles in BPD.Materials:Selection 65 cases preterm children from our hospital newborn NICU from October 2009 to January 2010. Inclusion criteria:BPD group of children less than 37 weeks gestational age, history of mechanical ventilation in the treatment within 1 week after birth,duration≥15 days, had a high oxygen inhalation history; control group, children less than 37 weeks gestational age, no ventilation treatment history, no history of high-oxygen inhalation. The amount of blood sample collected was about 1.5ml, a total of 34 cases in BPD group; 31 cases of control group; lung tissue were collected from 3 cases of the BPD group and control group 3 patients. Lung tissues were collected when parents were informed consent and agreed to its license.Methods:Serum collection:Acquisition of venous blood and injection in PC A tube, put it aside at room temperature for 30min before 1200rpm centrifuge 15min, the supernatant obtained and transferred to the high-pressure pipe,labeled and stored -20℃refrigerator; lung tissue collection:stillbirths lung tissue were picked about 1.5cm×1.5cm by location, stored in 10% formalin, stored at room temperature. TGF-β1 in serum were detect by enzyme-linked immunosorbent assay (ABC-ELISA), and the levels in lung samples were detect by using HE staining, immunohistochemistry and immunofluorescence.Results 1. Serum TGF-β1 expression of BPD group (9819.1±5540.1pg/ml) was significantly higher than control group (5952.7±2666.0pg/ml), there are statistical differences between the two groups (P< 0.05).2. Lung tissue test showed immunohistochemical staining area and intensity of BPD group greater than the control group, IPP image analysis system showed that BPD group mean optical density (mean density) (0.245±0.152) significantly higher than control group (0.116±0.073), (P<0.05).3. Immunofluorescence test showed that the fluorescence of lung alveolar epithelial cells in BPD group was higher than that in control group.Conclusion:1. The expression of TGF-β1 protein increased in BPD group which promoted the progression of pulmonary fibrosis, campared with control group.
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